Trans-autophosphorylation of ERBB2 homodimer

Stable Identifier
R-HSA-1248694
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
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Trans-autophosphorylation of ERBB2 homodimer
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ERBB2 homodimers trans-autophosphorylate to form phosphorylated ERBB2 that activates downstream signaling cascades (Hazan et al. 1990, Ricci et al. 1995, Pickl and Ries 2009, Maadi et al. 2018). The best characterized trans-autophophosphorylation sites in ERBB2 heterodimers are tyrosines Y1023, Y1139, Y1196, Y1221, Y1222 and Y1248. Studies of ERBB2 homodimers have not investigated trans-autophosphorylated tyrosines of ERBB2 comprehensively. Instead, each study reported a subset of trans-autophosphorylation sites:
Y1023 and Y1248 (Hazan et al. 1990);
Y1139, Y1221 and Y1248 (Ricci et al. 1995);
Y1248 (Pickl and Ries 2009);
Y1139 and Y1248 (Maadi et al. 2018) – this study also identified Y1005, Y1112, Y1127 and Y1196 as trans-autophosphorylation sites.
For ERBB2 homodimers, six canonical sites (Y1023, Y1139, Y1196, Y1221, Y1222 and Y1248) have been annotated as trans-autophosphorylation sites. This information will be revised as more experimental data becomes available.
Literature References
PubMed ID Title Journal Year
18978815 Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab

Pickl, M, Ries, CH

Oncogene 2009
29490608 The effects of trastuzumab on HER2-mediated cell signaling in CHO cells expressing human HER2

Nami, B, Wang, Z, Maadi, H, Li, G, Tong, J

BMC Cancer 2018
7478576 Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase

Pertica, C, Belardo, G, Natali, PG, Chiari, R, Lanfrancone, L, Segatto, O, Pelicci, PG, Ricci, A

Oncogene 1995
1706616 Identification of autophosphorylation sites of HER2/neu

Schlessinger, J, Zilberstein, A, Hazan, R, Ullrich, A, Dombalagian, M, Margolis, B

Cell Growth Differ 1990
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of ERBB2 homodimer [plasma membrane]

Physical Entity
ERBB2 homodimer [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
This event is regulated
Negatively by
Regulator
ERBB2:TKIs:ERBIN:HSP90:CDC37 [plasma membrane] (Homo sapiens)
Active Unit
lapatinib, neratinib, afatinib, AZ5104, tesevatinib, canertinib, sapitinib, CP-724714, AEE78 [cytosol]
Regulator
ERBB2:trastuzumab:ERBIN:HSP90:CDC37 [plasma membrane] (Homo sapiens)
Active Unit
trastuzumab [extracellular region]
Normal reaction
Trans-autophosphorylation of ERBB2 heterodimers (Homo sapiens)
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2019-07-31)
Reviewed
Kancha, RK  (2019-09-16)
Created
Orlic-Milacic, M  (2011-04-13)
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